Dihydroberberine demonstrates significant therapeutic effects in metabolic disorders, including lipid profile modulation, insulin sensitivity enhancement, and non-alcoholic fatty liver disease improvement. Concurrently, it exhibits cardiovascular protective effects by attenuating atherosclerotic progression and improving endothelial function. Pharmacokinetic studies reveal superior properties compared to its parent compound Berberine, notably higher bioavailability, enhanced tissue distribution, and prolonged elimination half-life. Clinical trials have confirmed its favorable safety profile, with phase II hyperlipidemia studies demonstrating therapeutic potential. Ongoing phase III diabetic nephropathy and phase II Alzheimer's disease investigations further support its translational value, particularly for metabolic syndrome management and cardiovascular disease prevention.

Pharmacological action

-Hypoglycaemic effect

Dihydroberberine is an alkaloid with significant hypoglycaemic activity, which can play an effective glucose control role by enhancing insulin sensitivity, inhibiting hepatic glucose production, regulating intestinal microecology and delaying sugar absorption. Animal experiments confirmed that compared with the model group, the medium and high dose groups of Dihydroberberine could significantly reduce the blood glucose level of rats at various time points after meals.

Figure 1 Analysis of the results of the oral glucose tolerance test (OGTT) in rats in each group.

-Weight management and body fat regulation

Dihydroberberine, as a hydrogenated derivative of Berberine, can regulate lipid metabolism through multiple targets, and has potential application value in improving obesity and related metabolic disorders. Several studies have shown that Dihydroberberine can not only reduce fat mass (including epididymal fat mass and inguinal fat mass) more effectively, but also reduce triglyceride levels in muscle tissue and liver tissue. Animal studies have shown that only 100 mg/kg of Dihydroberberine can have a similar fat loss effect to 560 mg/kg of Berberine.

Figure 2 Effect of Dihydroberberine on epididymal fat mass induced by a high-fat diet in obese mice.

-Anticancer

Due to its stronger tissue permeability and low toxicity, Dihydroberberine exerts anti-cancer effects in a variety of cancer models by inhibiting tumour proliferation, inducing apoptosis, blocking metastasis, and modulating the immune microenvironment. Studies have shown that the combination of Dihydroberberine and Sunitinib, a novel multi-targeted oral drug for the treatment of tumours, can produce synergistic anti-tumour effects and effectively inhibit the proliferation activity of NCI-H460 cells in non-small cell lung cancer in vitro.

Figure 3 Inhibition of cell proliferation of NCI-H460 cells after 48 hours of treatment with Dihydroberberine and/or Sunitinib.

-Anti-colitis

Dihydroberberine has shown great potential in the treatment of inflammatory bowel disease, where it exerts anti-inflammatory effects by inhibiting inflammatory responses, repairing the intestinal barrier, and regulating intestinal flora. The study confirmed that Dihydroberberine exerts a protective effect by alleviating the symptoms of ulcerative colitis induced by dextran sodium sulfate (DSS), down-regulating the Disease Activity Index (DAI) score, while significantly restoring the symptoms of shortened colon length induced by DSS exposure.

Figure 4 Effect of Dihydroberberine on disease activity in DSS-induced ulcerative colitis mice. (A) DAI score. (B) Colonic length measurements.

-Supports cardiovascular health

Dihydroberberine, as a typical isoquinoline alkaloid, has a significant protective effect on the cardiovascular and cerebrovascular system, which can protect the vascular endothelial function, inhibit the process of atherosclerosis, reduce the damage caused by myocardial ischaemia and reperfusion, and optimise the myocardial energy metabolism process. Studies have shown that it is more effective in reducing the size of atherosclerotic plaques and improving plaque stability than berberine, exhibiting a better cardiovascular protective effect.

Figure 5 Effect of Dihydroberberine on areas of atherosclerotic plaques.

-Neuroprotection

Dihydroberberine not only inherits the multiple functional properties of Berberine, but also highlights its special advantages in the field of neuroprotection due to its optimised pharmacokinetic characteristics and breakthrough blood-brain barrier penetration ability. Studies have shown that Dihydroberberine treatment can significantly reduce serum uric acid (SUA), blood urea nitrogen (BUN) levels and serum creatinine (Cr) content after one week of treatment, thereby improving the metabolic abnormalities of potassium oxyazinate/hypoxanthine (PO/HX)-induced hyperuricaemia in mice.

Figure 6 Effects of Dihydroberberine on UA, Cr and BUN in mice with PO/HX-induced hyperuricemia. (A) UA level. (B) BUN level. (C) Cr level.

-Other effects

Relevant studies have confirmed that Dihydroberberine, as a modified derivative of Berberine, shows multiple pharmacological activities in regulating blood lipid metabolism (by regulating lipid metabolising enzyme activity), scavenging free radicals and enhancing antioxidant enzyme activity, and destroying the cell membrane structure of microorganisms. Dihydroberberine has better pharmacodynamic characteristics and safety than the parent berberine in improving liver lipid metabolism abnormalities and has significant antioxidant and broad-spectrum antibacterial effects, showing good clinical application prospects.

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